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COMPOUNDING RECORDS AND
VERIFICATION
DOCUMENTS
Formulation Record, Compounding Record,
MSDS File
State boards of pharmacy have record keeping
requirements that must be met. The following are
practical for quality purposes and to enable another
compounder to duplicate the preparation when prepared at a later time.
The formulation record generally will be either on
the computer system, or may be an individual new
prescription or request. This is where the process
starts. The formulation record can be used to prepare the documentation for the compounding
record.
The compounding record contains the sources and lot
numbers of the ingredients, calculations, processes
used, results of any testing done, an assigned
beyond-use date, identification numbers, name of
the compounder, quantity of the preparation compounded and other pertinent information. It contains
all relevant information related to the actual compounding of the specific prescription. It is used for
checking the final preparation for accuracy.
Material Safety Data Sheets (MSDSs) may be either
hard copy or accessible electronically. They are
needed for all drug substances or bulk chemicals
located in the compounding pharmacy. If commercial products are used, the package insert can serve
this purpose.
QUALITY CONTROL
All the paperwork from the first step to the final
preparation should be reviewed along with observing the finished preparation.
Standard Operating Procedures (SOPs) are documents that describe how to perform routine tasks in
the environment of formulation development, purchasing, compounding, testing, maintenance,
materials handling, quality assurance and dispensing. They contain step-by-step instructions to
perform tasks reliably and consistently; including
how a task will be performed, who will do the task,
who is responsible, why it will be performed and
any limits associated with the task.
Verification, not validation, is what is required. Verification involves checking to ensure that all the
processes were appropriate and accurately performed. Validation is much more involved and
time-consuming.
PATIENT COUNSELING
As with any prescription, patient counseling is
important. It is especially important with compounded preparations where the beyond-use date
may be rather short. Patients should be counseled
about use, storage and evidence of instability (visual changes, odor, etc.).
SUMMARY
There is no question that the standards of the USP
serve to enhance patient safety and also protect the
pharmacist. There are many general chapters in the
USP that either directly or indirectly affect pharmacy compounding. The primary chapters are <795>
Pharmaceutical Compounding-Nonsterile Preparations, <797> Pharmaceutical Compounding
Compounding-Sterile Preparations, <1075> Good
Compounding Practices, and <1160> Pharmaceutical Calculations in Prescription Compounding.
In the next issue, we will discuss the rationale
behind and the practical application of USP <797>.
2. U.S. Pharmacopoeial Convention, Inc. USP-Pharmacists’ Pharmacopeia, Rockville MD, U.S.
Pharmacopeial Convention, Inc., 2005, pp 408-413.
2. Today, the USP/NF standards are applicable to:
I.
pharmaceutical companies
II.
compounding pharmacies
III. health food/nutrition stores
A. I only
B.
III only
C.
I and II only
D. II and III only
E.
I, II and III.
7.
8.
3. The USP began to reorient its activities to include pharmacy
compounding again in:
A. 1965
B.
1970
C.
1975
D. 1980
E.
1985
4. The terminology applied to compounded prescriptions and the date
after which they should not be used are:
A. products, expiration date
B.
products, beyond use date
C.
preparations, expiration date
D. preparations, beyond use date
E.
none of the above
5. The ultimate responsibility for compliance with all the USP/NF
standards for compounding rest with the:
A. prescribing physician
B.
owner
C.
compounder
D. technician
E.
all the above
6. If no valid data is available for an aqueous, oral compounded suspension, the beyond use date to be applied is:
A. 24 hours at room temperature
B.
72 hours at refrigerated temperature
C.
1 week at room temperature
D. 2 weeks at refrigerated temperature
E.
6 months at refrigerated temperature
Which of the following is NOT on the checklist for acceptable strength,
quality and purity?
A. Have the physical and chemical properties and medicinal, dietary, and
pharmaceutical uses of the drug substances been reviewed?
B. Are the quantity and quality of each active ingredient identifiable?
C. Will the active ingredients be effectively absorbed, locally or systemically according to the prescribed purpose, from the preparation and
route of administration?
D. Has the bioavailability of the compounded preparation been demonstrated?
E. Were all calculations and measurements confirmed to ensure
that the preparation will be compounded accurately?
The purposes of the thirteen steps in the Compounding Process are to:
I. minimize errors
II. maximize the prescribers’ intent for the patient
III. provide shortcuts in compounding
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
9.
Which of the following records is where the information concerning
the ingredients used in compounding a prescription, such as the manufacturer, lot numbers, expiration dates of chemicals, are recorded?
A. formulation record
B. compounding record
C. material safety data sheet
D. certificate of analysis
E. none of the above
10. The purpose of the compounding standards of the USP are to:
I. ensure third party reimbursement
II. enhance patient safety
III. protect the pharmacist
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
11. My practice setting is:
a. Community-based
c. Hospital-based
b. Managed care-based
d. Consultant and other
12. The quality of the information presented in this article was:
a. Excellent b. Good
c. Fair d. Poor
13. The test questions correspond well with the information presented.
a. Yes
b. No
14. Approximately how long did it take you to read the Secundum Artem
article AND respond to the test questions?
______________________________________________________________
15. What topics would you like to see in future issues of Secundum Artem?
______________________________________________________________
Please print address clearly below OR
affix an address label here if available
Date__________________________
Name_____________________________________________________________________________________________________
Home Address _____________________________________________________________________________________________
City______________________________________________State______________ Zip___________________________________
Secundum
Artem
Current & Practical Compounding
Information for the Pharmacist.
USP Chapter <795>
Pharmaceutical Compounding - Nonsterile Preparations
GOALS AND OBJECTIVES
Goal: The goal of this article is to provide information on the historical development and practical implementation
of USP Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations.
Objectives: After reading and studying the article, the reader will be able to:
1. Discuss the history and development of the USP-NF and the USP-Pharmacists’ Pharmacopeia.
2. List the five questions that should be considered concerning each compounded prescription.
3. Discuss the difference between a “product” and a “preparation” as well as the difference between an “expiration date”
and a “beyond use date”.
4. Discuss the various sections of USP Chapter <795> and their application.
5. List the two basic reasons or intent for developing USP Chapter <795>.
INTRODUCTION
What is USP Chapter <795>? Why should compounders be familiar with it? Where did it come from?
From where did it derive its authority? Do I have to
follow it? What happens if I don’t? Is it really important? What if I have never had a problem before……do
I still need to comply with its standards? Who establishes these standards? Are they “set in stone” or do
they change over time? What is the relationship
between the USP and the U.S. government? What is
the relationship between the USP and the Food and
Drug Administration? Do the USP standards really
contribute to patient safety?
Primary State Licensure _____________________________________________________________________________________
License No._________________________________________________________________________________________________
Home Phone (
Copies of the individual USP Chapter <795>
Pharmaceutical Compounding-Nonsterile
Preparations or the new USP-Pharmacists’
Pharmacopeia, can be obtained online at
www.usp.org or by calling 1-800-227-8772.
NUMBER 4
Please circle the most appropriate answer for each of the following questions. There is only ONE correct answer per question.
1. The first U.S. Pharmacopeia was established in 1820 by a group of:
A. pharmacists.
B.
physicians.
C.
government agents.
D. state boards.
E.
physicians and dentists.
REFERENCES
1. Allen Jr LV, Popovich NG, Ansel HC. Ansel’s
Pharmaceutical Dosage Forms and Drug Delivery
Systems, 8th Ed. Baltimore MD, Lippincott,
Williams & Wilkins, 2005, pp 7-12.
VOLUME 13
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To receive credit, send completed registration form and test answer sheet (original or a photocopy of the page), *to: QUEST
EDUCATIONAL SERVICES, INC., P.O. BOX 1092, GROTON, CT 06340. One contact hour (0.1 CEU) awarded for a passing grade
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completed by others and duplicated for others will be graded.
All these are valid questions that deserve an answer.
As we travel from looking at where the pharmacopeias
came from and from where they derive their authority,
we will look at how the USP-NF shapes pharmacy
compounding and the pharmaceutical industry today.
Loyd V. Allen, Jr., Ph.D., R.Ph., Professor Emeritus,
University of Oklahoma, HSC College of Pharmacy,
Oklahoma City, OK 73190
Two things to keep in mind regarding the USP and
these chapters; the intent is to protect both the patient
AND the pharmacist. Protection of the patient is
addressed when these standards are followed and the
pharmacist when any adverse event might occur where
patient harm and/or litigation results.
BACKGROUND
Pharmaceutical compounding is the history of pharmacy,
spanning the past 5,000 years, until the early to mid
1900s when the pharmaceutical industry came into
being. There are many recorded writings of formulas
and methods of treating disease in pharmacy history
books. The standards for uniformity and quality in
pharmacy compounding started back in 1580 in Bergamo,
Italy, where the term “pharmacopoeia” was first used in
connection with a local book of drug standards. Many
pharmacopeias were developed on local, city and
Quest Educational Services Inc. is accredited by the
Accreditation Council for Pharmacy Education as a
provider of continuing pharmaceutical education.
ACPE No. 748-000-05-001-H01 (0.1 CEU)
This lesson is no longer valid for CE credit after 12/01/08.
national levels in Europe. Some of the best known were
the London, Edinburgh and Dublin Pharmacopeias
which were official until 1864, when they were combined and replaced by the well-known British
Pharmacopeia.1
the USP purchased the NF and in 1980 the first combined USP-NF was published and continually
published the book every 5 years. In 2002, annual revisions were implemented. Today the USP-NF is
published on an annual basis. 1
The U.S. Pharmacopeia (USP) was established in January 1820 by a group of physicians from the United States
at the first Pharmacopeial convention. The objective of
the USP was to establish uniform standards for the
medications they prescribed. In December 1820, they
published the first U.S. Pharmacopeia. Following this,
the USP convention met every 10 years and produced a
revision to the book; pharmacists were invited to join in
1850. 1
There was a change in the USP during the early-mid
1900s as the pharmaceutical industry began to grow
and assume a major role in providing pharmaceuticals
to the public. The USP changed its format from an orientation towards compounded pharmaceuticals to
manufactured pharmaceuticals. This change continued
throughout the 1900s and early into the 2000s. Also,
during the 1800s and 1900s, the State Boards of Pharmacy enforced the standards of the USP and NF in
pharmacies at the state level. However, as compounding diminished, the state boards did not necessarily
require USP or NF volumes actually be in the required
library of the pharmacies.
The USP is an independent organization where decisions about standards are made by the many volunteers
serving on various expert committees. There are two
committees that address compounding; one for nonsterile and one for sterile activities. Each committee consists
of 10 to 12 volunteers from pharmacy practice, academia and related support companies. The expert
committees meet with sufficient frequency to accomplish their goals (usually one to three times per year)
and conduct much of their business via telephone,
e-mails, etc. Each committee has a staff liaison at USP
that is responsible for working with the committees.
The USP was mentioned as a “standard” in the Drug
Importation Act of 1848 and the USP and NF were both
established as official compendia for the United States
in the Pure Food and Drug Act of 1906. Its’ status continues today. In 1938, the Food and Drug
Administration (FDA) was born, having originally been
the US Department of Agriculture Bureau of Chemistry,
then the Food, Drug and Insecticide Administration and
finally the FDA. The FDA can enforce the standards
established by the USP for the pharmaceutical industry
or the standards it develops. The USP is independent
and has no relationship with either the federal government or the FDA. It is unique because other
pharmacopoeias throughout the world are prepared by
the government of the country, but not the USP. 1
The National Formulary (NF) was first published in 1888
by the American Pharmaceutical Association, listing
standardized formulas including the ingredients and
their quantities required for compounding purposes. 1
In 1940, the USP changed from the 10-year to a 5-year
meeting cycle to adapt more rapidly to change. In 1975
However, in the 1970s, there was a resurgence of pharmacy compounding and in 1985, the USP Convention
passed two resolutions urging the USP to become
active again in promoting standards for pharmacy
compounding. This was followed with convention resolutions in 1990, 1995 and again in 2000.
In 1993, there was the formation of the Expert Advisory Panel and the Review Panel on Pharmacy
Compounding Practices by the USP. The Expert Advisory Panel is divided into two groups; one to work on
general chapters and the other to work on compounding monographs. In 1996, the USP published the
chapter Pharmacy Compounding Practices <1161> to
provide guidance to pharmacists and other compounding professionals on proper compounding practices
and techniques.
When Congress enacted the FDA Modernization Act of
1997 (FDAMA97) that referred to pharmacy compounding, the FDA formed an internal FDA Steering
Committee and an external FDA Compounding Advisory Committee to aid in implementing the
compounding provisions of FDAMA97. Since
FDAMA97 referred to USP and the enforceability of its
contents, it was deemed necessary to renumber <1161>
Pharmacy Compounding Practices from an informational chapter (numbered >1000), to <795> an
enforceable chapter (numbered <1000) and ultimately
its name was changed to Pharmaceutical Compounding-Nonsterile Preparations. It became official in
January 2000 and remains so today.
In the mid-1990s, those involved with the USP pharmacy compounding activities saw the need to reorient
part of the USP-NF back to pharmacy. It was evident
that the regular USP-NF had grown so much and was
so entrenched in the pharmaceutical industry, but yet
much of it still applied to pharmacy practice. It was
then that the idea of a separate compendium was born.
In July 2005, the long-awaited USP-Pharmacists’ Pharmacopoeia was published, containing official and
authorized information for pharmacists.
TAKE A TOUR THROUGH <795>
2
Walking through USP <795>, the first thing that is discussed is the responsibility of the compounder (which
covers pharmacists, physicians, etc.). One has to have
a facility in which to practice that meets certain minimum standards as well as equipment. One must also
know about the stability of the compounded preparations and what kind of beyond-use date can be placed
on the preparations. The next item concerns the selection of ingredients and their quality. There is a
checklist that should be considered before compounding and then a discussion of procedures for different
dosage forms. The compounding process is discussed
as well as necessary records and documentation. The
chapter concludes with short discussions on quality
control, verification and patient counseling.
Before we look at some details, let’s go over some terminology. We have “manufactured products” and
“compounded preparations”; this distinguishes
between the output of the pharmaceutical companies
(products) and the pharmacies (preparations). Pharmacists compound “preparations”; the pharmaceutical
industry manufactures “products”. Also, products
have “expiration dates” that are determined through
extensive laboratory experimentation, statistical analysis, etc. Compounded preparations have “beyond-use
dates” which are conservative reasonable estimates.
Let’s briefly review the intent and/or emphasis of the
various sections of <795>.
RESPONSIBILITY OF THE COMPOUNDER
The buck stops here! The primary emphasis on the
responsibility of the compounder centers around assurance of quality in the areas of personnel, ingredients,
finished preparations, processes, environment, stability, consistency, error-prevention and documentation.
FACILITY AND EQUIPMENT
Facilities and Equipment
The primary requirement here is adequate and appropriate space. These requirements are similar to those
mandated by the state boards of pharmacy.
Equipment must simply be appropriate in design and size
and suitable for the purpose for which it is used. It should
not interact or interfere with the compounded preparation
or process. It must be properly maintained, used, calibrated and cleaned.
STABILITY OF COMPOUNDED PREPARATIONS
Primary Packaging, Stability Criteria and Beyond-Use
Dating, Beyond-Use Labeling
The beyond-use date is the responsibility of the compounder and is determined from the time of
compounding, not the time of dispensing. Compounders
can consult appropriate literature, manufacturers and
work with analytical laboratories to determine an appropriate beyond-use date. In the event there is no data
available, the chapter provides guidelines that can be
used, as follows: 2
●
Solids and non-aqueous liquids prepared from commercially available dosage forms - 25% of the remaining
expiration date of the commercial product, or 6 months,
whichever is earlier.
●
Solids and non-aqueous liquids prepared from bulk
ingredients - up to 6 months.
●
Water-containing formulations (prepared from ingredients in solid form) - up to 14 days when stored in a
refrigerator.
●
All other formulations - up to 30 days or the intended
duration of therapy, whichever is earlier.
DEFINITIONS
The purpose of this section is merely to provide a definition for some terms used in the chapter.
INGREDIENT SELECTION
Sources
First and foremost, USP and NF grade ingredients should
be used. If an item is not monographed in the USP or NF,
then the pharmacist must select a reasonable highquality grade ingredient from a reliable source.
Certificates of analysis can be useful in establishing
quality of the ingredients used, both active and
excipients. Items not to be compounded are those on
the FDA negative list. However, one must read the
negative list very carefully because in some cases, it
is not all dosage forms of an active drug, but just a
specific dosage form that is on the list and other
dosage forms can be prepared.
CHECKLIST FOR ACCEPTABLE
STRENGTH, QUALITY AND PURITY
A series of five questions are presented for consideration concerning each and every compounded
preparation. While some of these questions are second
nature, some may require some thought and even
investigation, such as those related to local or systemic absorption. These questions are as follows: 2
1. Have the physical and chemical properties and
medicinal, dietary, and pharmaceutical uses of
the drug substances been reviewed?
2. Are the quantity and quality of each active ingredient identifiable?
3. Will the active ingredients be effectively
absorbed, locally or systemically according to
the prescribed purpose, from the preparation
and route of administration?
4. Are there added substances, confirmed or potentially present from manufactured products, that
may be expected to cause an allergic reaction,
irritation, toxicity, or undesirable organoleptic
response from the patient? Are there added substances, confirmed or potentially present, that
may be unfavorable (e.g., unsuitable pH or inadequate solubility)?
5. Were all calculations and measurements confirmed to ensure that the preparation will be
compounded accurately?
COMPOUNDED PREPARATIONS
Quality suggestions, clinical considerations and
technical procedural hints are provided for solid, liquid and semisolid dosage forms.
COMPOUNDING PROCESS
Thirteen steps are presented to minimize error and
maximize the prescriber’s intent for the patient.
These should all be covered in the standard operating
procedures of the pharmacy and are good practice
standards to follow. The steps are as follows: 2
1. Judge the suitability of the prescription to be
compounded in terms of its safety and intended
use. Determine what legal limitations, if any,
are applicable.
2. Perform necessary calculations to establish the
amounts of ingredients needed.
3. Identify equipment needed.
4. Wear the proper attire and wash hands.
5. Clean the compounding area and needed
equipment.
6. Only one prescription should be compounded
at one time in a specified compounding area.
7. Assemble all necessary materials to compound
the prescription.
8. Compound the preparation following the formulation record or prescription, according to
the art and science of pharmacy.
9. Assess weight variation, adequacy of mixing,
clarity, odor, color, consistency and pH as
appropriate.
10. Annotate the compounding log, and describe
the appearance of the formulation.
11. Label the prescription containers to include the
following items:
a) The name of the preparation
b) The internal identification number
c) The beyond-use date
d) The initials of the compounder who
prepared the label
e) Any storage requirements
f) Any other statements required by law.
12. Sign and date the prescription affirming that all
procedures were carried out to ensure uniformity, identity, strength, quantity, and purity.
13. Thoroughly and promptly clean all equipment,
and store properly.
national levels in Europe. Some of the best known were
the London, Edinburgh and Dublin Pharmacopeias
which were official until 1864, when they were combined and replaced by the well-known British
Pharmacopeia.1
the USP purchased the NF and in 1980 the first combined USP-NF was published and continually
published the book every 5 years. In 2002, annual revisions were implemented. Today the USP-NF is
published on an annual basis. 1
The U.S. Pharmacopeia (USP) was established in January 1820 by a group of physicians from the United States
at the first Pharmacopeial convention. The objective of
the USP was to establish uniform standards for the
medications they prescribed. In December 1820, they
published the first U.S. Pharmacopeia. Following this,
the USP convention met every 10 years and produced a
revision to the book; pharmacists were invited to join in
1850. 1
There was a change in the USP during the early-mid
1900s as the pharmaceutical industry began to grow
and assume a major role in providing pharmaceuticals
to the public. The USP changed its format from an orientation towards compounded pharmaceuticals to
manufactured pharmaceuticals. This change continued
throughout the 1900s and early into the 2000s. Also,
during the 1800s and 1900s, the State Boards of Pharmacy enforced the standards of the USP and NF in
pharmacies at the state level. However, as compounding diminished, the state boards did not necessarily
require USP or NF volumes actually be in the required
library of the pharmacies.
The USP is an independent organization where decisions about standards are made by the many volunteers
serving on various expert committees. There are two
committees that address compounding; one for nonsterile and one for sterile activities. Each committee consists
of 10 to 12 volunteers from pharmacy practice, academia and related support companies. The expert
committees meet with sufficient frequency to accomplish their goals (usually one to three times per year)
and conduct much of their business via telephone,
e-mails, etc. Each committee has a staff liaison at USP
that is responsible for working with the committees.
The USP was mentioned as a “standard” in the Drug
Importation Act of 1848 and the USP and NF were both
established as official compendia for the United States
in the Pure Food and Drug Act of 1906. Its’ status continues today. In 1938, the Food and Drug
Administration (FDA) was born, having originally been
the US Department of Agriculture Bureau of Chemistry,
then the Food, Drug and Insecticide Administration and
finally the FDA. The FDA can enforce the standards
established by the USP for the pharmaceutical industry
or the standards it develops. The USP is independent
and has no relationship with either the federal government or the FDA. It is unique because other
pharmacopoeias throughout the world are prepared by
the government of the country, but not the USP. 1
The National Formulary (NF) was first published in 1888
by the American Pharmaceutical Association, listing
standardized formulas including the ingredients and
their quantities required for compounding purposes. 1
In 1940, the USP changed from the 10-year to a 5-year
meeting cycle to adapt more rapidly to change. In 1975
However, in the 1970s, there was a resurgence of pharmacy compounding and in 1985, the USP Convention
passed two resolutions urging the USP to become
active again in promoting standards for pharmacy
compounding. This was followed with convention resolutions in 1990, 1995 and again in 2000.
In 1993, there was the formation of the Expert Advisory Panel and the Review Panel on Pharmacy
Compounding Practices by the USP. The Expert Advisory Panel is divided into two groups; one to work on
general chapters and the other to work on compounding monographs. In 1996, the USP published the
chapter Pharmacy Compounding Practices <1161> to
provide guidance to pharmacists and other compounding professionals on proper compounding practices
and techniques.
When Congress enacted the FDA Modernization Act of
1997 (FDAMA97) that referred to pharmacy compounding, the FDA formed an internal FDA Steering
Committee and an external FDA Compounding Advisory Committee to aid in implementing the
compounding provisions of FDAMA97. Since
FDAMA97 referred to USP and the enforceability of its
contents, it was deemed necessary to renumber <1161>
Pharmacy Compounding Practices from an informational chapter (numbered >1000), to <795> an
enforceable chapter (numbered <1000) and ultimately
its name was changed to Pharmaceutical Compounding-Nonsterile Preparations. It became official in
January 2000 and remains so today.
In the mid-1990s, those involved with the USP pharmacy compounding activities saw the need to reorient
part of the USP-NF back to pharmacy. It was evident
that the regular USP-NF had grown so much and was
so entrenched in the pharmaceutical industry, but yet
much of it still applied to pharmacy practice. It was
then that the idea of a separate compendium was born.
In July 2005, the long-awaited USP-Pharmacists’ Pharmacopoeia was published, containing official and
authorized information for pharmacists.
TAKE A TOUR THROUGH <795>
2
Walking through USP <795>, the first thing that is discussed is the responsibility of the compounder (which
covers pharmacists, physicians, etc.). One has to have
a facility in which to practice that meets certain minimum standards as well as equipment. One must also
know about the stability of the compounded preparations and what kind of beyond-use date can be placed
on the preparations. The next item concerns the selection of ingredients and their quality. There is a
checklist that should be considered before compounding and then a discussion of procedures for different
dosage forms. The compounding process is discussed
as well as necessary records and documentation. The
chapter concludes with short discussions on quality
control, verification and patient counseling.
Before we look at some details, let’s go over some terminology. We have “manufactured products” and
“compounded preparations”; this distinguishes
between the output of the pharmaceutical companies
(products) and the pharmacies (preparations). Pharmacists compound “preparations”; the pharmaceutical
industry manufactures “products”. Also, products
have “expiration dates” that are determined through
extensive laboratory experimentation, statistical analysis, etc. Compounded preparations have “beyond-use
dates” which are conservative reasonable estimates.
Let’s briefly review the intent and/or emphasis of the
various sections of <795>.
RESPONSIBILITY OF THE COMPOUNDER
The buck stops here! The primary emphasis on the
responsibility of the compounder centers around assurance of quality in the areas of personnel, ingredients,
finished preparations, processes, environment, stability, consistency, error-prevention and documentation.
FACILITY AND EQUIPMENT
Facilities and Equipment
The primary requirement here is adequate and appropriate space. These requirements are similar to those
mandated by the state boards of pharmacy.
Equipment must simply be appropriate in design and size
and suitable for the purpose for which it is used. It should
not interact or interfere with the compounded preparation
or process. It must be properly maintained, used, calibrated and cleaned.
STABILITY OF COMPOUNDED PREPARATIONS
Primary Packaging, Stability Criteria and Beyond-Use
Dating, Beyond-Use Labeling
The beyond-use date is the responsibility of the compounder and is determined from the time of
compounding, not the time of dispensing. Compounders
can consult appropriate literature, manufacturers and
work with analytical laboratories to determine an appropriate beyond-use date. In the event there is no data
available, the chapter provides guidelines that can be
used, as follows: 2
●
Solids and non-aqueous liquids prepared from commercially available dosage forms - 25% of the remaining
expiration date of the commercial product, or 6 months,
whichever is earlier.
●
Solids and non-aqueous liquids prepared from bulk
ingredients - up to 6 months.
●
Water-containing formulations (prepared from ingredients in solid form) - up to 14 days when stored in a
refrigerator.
●
All other formulations - up to 30 days or the intended
duration of therapy, whichever is earlier.
DEFINITIONS
The purpose of this section is merely to provide a definition for some terms used in the chapter.
INGREDIENT SELECTION
Sources
First and foremost, USP and NF grade ingredients should
be used. If an item is not monographed in the USP or NF,
then the pharmacist must select a reasonable highquality grade ingredient from a reliable source.
Certificates of analysis can be useful in establishing
quality of the ingredients used, both active and
excipients. Items not to be compounded are those on
the FDA negative list. However, one must read the
negative list very carefully because in some cases, it
is not all dosage forms of an active drug, but just a
specific dosage form that is on the list and other
dosage forms can be prepared.
CHECKLIST FOR ACCEPTABLE
STRENGTH, QUALITY AND PURITY
A series of five questions are presented for consideration concerning each and every compounded
preparation. While some of these questions are second
nature, some may require some thought and even
investigation, such as those related to local or systemic absorption. These questions are as follows: 2
1. Have the physical and chemical properties and
medicinal, dietary, and pharmaceutical uses of
the drug substances been reviewed?
2. Are the quantity and quality of each active ingredient identifiable?
3. Will the active ingredients be effectively
absorbed, locally or systemically according to
the prescribed purpose, from the preparation
and route of administration?
4. Are there added substances, confirmed or potentially present from manufactured products, that
may be expected to cause an allergic reaction,
irritation, toxicity, or undesirable organoleptic
response from the patient? Are there added substances, confirmed or potentially present, that
may be unfavorable (e.g., unsuitable pH or inadequate solubility)?
5. Were all calculations and measurements confirmed to ensure that the preparation will be
compounded accurately?
COMPOUNDED PREPARATIONS
Quality suggestions, clinical considerations and
technical procedural hints are provided for solid, liquid and semisolid dosage forms.
COMPOUNDING PROCESS
Thirteen steps are presented to minimize error and
maximize the prescriber’s intent for the patient.
These should all be covered in the standard operating
procedures of the pharmacy and are good practice
standards to follow. The steps are as follows: 2
1. Judge the suitability of the prescription to be
compounded in terms of its safety and intended
use. Determine what legal limitations, if any,
are applicable.
2. Perform necessary calculations to establish the
amounts of ingredients needed.
3. Identify equipment needed.
4. Wear the proper attire and wash hands.
5. Clean the compounding area and needed
equipment.
6. Only one prescription should be compounded
at one time in a specified compounding area.
7. Assemble all necessary materials to compound
the prescription.
8. Compound the preparation following the formulation record or prescription, according to
the art and science of pharmacy.
9. Assess weight variation, adequacy of mixing,
clarity, odor, color, consistency and pH as
appropriate.
10. Annotate the compounding log, and describe
the appearance of the formulation.
11. Label the prescription containers to include the
following items:
a) The name of the preparation
b) The internal identification number
c) The beyond-use date
d) The initials of the compounder who
prepared the label
e) Any storage requirements
f) Any other statements required by law.
12. Sign and date the prescription affirming that all
procedures were carried out to ensure uniformity, identity, strength, quantity, and purity.
13. Thoroughly and promptly clean all equipment,
and store properly.
national levels in Europe. Some of the best known were
the London, Edinburgh and Dublin Pharmacopeias
which were official until 1864, when they were combined and replaced by the well-known British
Pharmacopeia.1
the USP purchased the NF and in 1980 the first combined USP-NF was published and continually
published the book every 5 years. In 2002, annual revisions were implemented. Today the USP-NF is
published on an annual basis. 1
The U.S. Pharmacopeia (USP) was established in January 1820 by a group of physicians from the United States
at the first Pharmacopeial convention. The objective of
the USP was to establish uniform standards for the
medications they prescribed. In December 1820, they
published the first U.S. Pharmacopeia. Following this,
the USP convention met every 10 years and produced a
revision to the book; pharmacists were invited to join in
1850. 1
There was a change in the USP during the early-mid
1900s as the pharmaceutical industry began to grow
and assume a major role in providing pharmaceuticals
to the public. The USP changed its format from an orientation towards compounded pharmaceuticals to
manufactured pharmaceuticals. This change continued
throughout the 1900s and early into the 2000s. Also,
during the 1800s and 1900s, the State Boards of Pharmacy enforced the standards of the USP and NF in
pharmacies at the state level. However, as compounding diminished, the state boards did not necessarily
require USP or NF volumes actually be in the required
library of the pharmacies.
The USP is an independent organization where decisions about standards are made by the many volunteers
serving on various expert committees. There are two
committees that address compounding; one for nonsterile and one for sterile activities. Each committee consists
of 10 to 12 volunteers from pharmacy practice, academia and related support companies. The expert
committees meet with sufficient frequency to accomplish their goals (usually one to three times per year)
and conduct much of their business via telephone,
e-mails, etc. Each committee has a staff liaison at USP
that is responsible for working with the committees.
The USP was mentioned as a “standard” in the Drug
Importation Act of 1848 and the USP and NF were both
established as official compendia for the United States
in the Pure Food and Drug Act of 1906. Its’ status continues today. In 1938, the Food and Drug
Administration (FDA) was born, having originally been
the US Department of Agriculture Bureau of Chemistry,
then the Food, Drug and Insecticide Administration and
finally the FDA. The FDA can enforce the standards
established by the USP for the pharmaceutical industry
or the standards it develops. The USP is independent
and has no relationship with either the federal government or the FDA. It is unique because other
pharmacopoeias throughout the world are prepared by
the government of the country, but not the USP. 1
The National Formulary (NF) was first published in 1888
by the American Pharmaceutical Association, listing
standardized formulas including the ingredients and
their quantities required for compounding purposes. 1
In 1940, the USP changed from the 10-year to a 5-year
meeting cycle to adapt more rapidly to change. In 1975
However, in the 1970s, there was a resurgence of pharmacy compounding and in 1985, the USP Convention
passed two resolutions urging the USP to become
active again in promoting standards for pharmacy
compounding. This was followed with convention resolutions in 1990, 1995 and again in 2000.
In 1993, there was the formation of the Expert Advisory Panel and the Review Panel on Pharmacy
Compounding Practices by the USP. The Expert Advisory Panel is divided into two groups; one to work on
general chapters and the other to work on compounding monographs. In 1996, the USP published the
chapter Pharmacy Compounding Practices <1161> to
provide guidance to pharmacists and other compounding professionals on proper compounding practices
and techniques.
When Congress enacted the FDA Modernization Act of
1997 (FDAMA97) that referred to pharmacy compounding, the FDA formed an internal FDA Steering
Committee and an external FDA Compounding Advisory Committee to aid in implementing the
compounding provisions of FDAMA97. Since
FDAMA97 referred to USP and the enforceability of its
contents, it was deemed necessary to renumber <1161>
Pharmacy Compounding Practices from an informational chapter (numbered >1000), to <795> an
enforceable chapter (numbered <1000) and ultimately
its name was changed to Pharmaceutical Compounding-Nonsterile Preparations. It became official in
January 2000 and remains so today.
In the mid-1990s, those involved with the USP pharmacy compounding activities saw the need to reorient
part of the USP-NF back to pharmacy. It was evident
that the regular USP-NF had grown so much and was
so entrenched in the pharmaceutical industry, but yet
much of it still applied to pharmacy practice. It was
then that the idea of a separate compendium was born.
In July 2005, the long-awaited USP-Pharmacists’ Pharmacopoeia was published, containing official and
authorized information for pharmacists.
TAKE A TOUR THROUGH <795>
2
Walking through USP <795>, the first thing that is discussed is the responsibility of the compounder (which
covers pharmacists, physicians, etc.). One has to have
a facility in which to practice that meets certain minimum standards as well as equipment. One must also
know about the stability of the compounded preparations and what kind of beyond-use date can be placed
on the preparations. The next item concerns the selection of ingredients and their quality. There is a
checklist that should be considered before compounding and then a discussion of procedures for different
dosage forms. The compounding process is discussed
as well as necessary records and documentation. The
chapter concludes with short discussions on quality
control, verification and patient counseling.
Before we look at some details, let’s go over some terminology. We have “manufactured products” and
“compounded preparations”; this distinguishes
between the output of the pharmaceutical companies
(products) and the pharmacies (preparations). Pharmacists compound “preparations”; the pharmaceutical
industry manufactures “products”. Also, products
have “expiration dates” that are determined through
extensive laboratory experimentation, statistical analysis, etc. Compounded preparations have “beyond-use
dates” which are conservative reasonable estimates.
Let’s briefly review the intent and/or emphasis of the
various sections of <795>.
RESPONSIBILITY OF THE COMPOUNDER
The buck stops here! The primary emphasis on the
responsibility of the compounder centers around assurance of quality in the areas of personnel, ingredients,
finished preparations, processes, environment, stability, consistency, error-prevention and documentation.
FACILITY AND EQUIPMENT
Facilities and Equipment
The primary requirement here is adequate and appropriate space. These requirements are similar to those
mandated by the state boards of pharmacy.
Equipment must simply be appropriate in design and size
and suitable for the purpose for which it is used. It should
not interact or interfere with the compounded preparation
or process. It must be properly maintained, used, calibrated and cleaned.
STABILITY OF COMPOUNDED PREPARATIONS
Primary Packaging, Stability Criteria and Beyond-Use
Dating, Beyond-Use Labeling
The beyond-use date is the responsibility of the compounder and is determined from the time of
compounding, not the time of dispensing. Compounders
can consult appropriate literature, manufacturers and
work with analytical laboratories to determine an appropriate beyond-use date. In the event there is no data
available, the chapter provides guidelines that can be
used, as follows: 2
●
Solids and non-aqueous liquids prepared from commercially available dosage forms - 25% of the remaining
expiration date of the commercial product, or 6 months,
whichever is earlier.
●
Solids and non-aqueous liquids prepared from bulk
ingredients - up to 6 months.
●
Water-containing formulations (prepared from ingredients in solid form) - up to 14 days when stored in a
refrigerator.
●
All other formulations - up to 30 days or the intended
duration of therapy, whichever is earlier.
DEFINITIONS
The purpose of this section is merely to provide a definition for some terms used in the chapter.
INGREDIENT SELECTION
Sources
First and foremost, USP and NF grade ingredients should
be used. If an item is not monographed in the USP or NF,
then the pharmacist must select a reasonable highquality grade ingredient from a reliable source.
Certificates of analysis can be useful in establishing
quality of the ingredients used, both active and
excipients. Items not to be compounded are those on
the FDA negative list. However, one must read the
negative list very carefully because in some cases, it
is not all dosage forms of an active drug, but just a
specific dosage form that is on the list and other
dosage forms can be prepared.
CHECKLIST FOR ACCEPTABLE
STRENGTH, QUALITY AND PURITY
A series of five questions are presented for consideration concerning each and every compounded
preparation. While some of these questions are second
nature, some may require some thought and even
investigation, such as those related to local or systemic absorption. These questions are as follows: 2
1. Have the physical and chemical properties and
medicinal, dietary, and pharmaceutical uses of
the drug substances been reviewed?
2. Are the quantity and quality of each active ingredient identifiable?
3. Will the active ingredients be effectively
absorbed, locally or systemically according to
the prescribed purpose, from the preparation
and route of administration?
4. Are there added substances, confirmed or potentially present from manufactured products, that
may be expected to cause an allergic reaction,
irritation, toxicity, or undesirable organoleptic
response from the patient? Are there added substances, confirmed or potentially present, that
may be unfavorable (e.g., unsuitable pH or inadequate solubility)?
5. Were all calculations and measurements confirmed to ensure that the preparation will be
compounded accurately?
COMPOUNDED PREPARATIONS
Quality suggestions, clinical considerations and
technical procedural hints are provided for solid, liquid and semisolid dosage forms.
COMPOUNDING PROCESS
Thirteen steps are presented to minimize error and
maximize the prescriber’s intent for the patient.
These should all be covered in the standard operating
procedures of the pharmacy and are good practice
standards to follow. The steps are as follows: 2
1. Judge the suitability of the prescription to be
compounded in terms of its safety and intended
use. Determine what legal limitations, if any,
are applicable.
2. Perform necessary calculations to establish the
amounts of ingredients needed.
3. Identify equipment needed.
4. Wear the proper attire and wash hands.
5. Clean the compounding area and needed
equipment.
6. Only one prescription should be compounded
at one time in a specified compounding area.
7. Assemble all necessary materials to compound
the prescription.
8. Compound the preparation following the formulation record or prescription, according to
the art and science of pharmacy.
9. Assess weight variation, adequacy of mixing,
clarity, odor, color, consistency and pH as
appropriate.
10. Annotate the compounding log, and describe
the appearance of the formulation.
11. Label the prescription containers to include the
following items:
a) The name of the preparation
b) The internal identification number
c) The beyond-use date
d) The initials of the compounder who
prepared the label
e) Any storage requirements
f) Any other statements required by law.
12. Sign and date the prescription affirming that all
procedures were carried out to ensure uniformity, identity, strength, quantity, and purity.
13. Thoroughly and promptly clean all equipment,
and store properly.
COMPOUNDING RECORDS AND
VERIFICATION
DOCUMENTS
Formulation Record, Compounding Record,
MSDS File
State boards of pharmacy have record keeping
requirements that must be met. The following are
practical for quality purposes and to enable another
compounder to duplicate the preparation when prepared at a later time.
The formulation record generally will be either on
the computer system, or may be an individual new
prescription or request. This is where the process
starts. The formulation record can be used to prepare the documentation for the compounding
record.
The compounding record contains the sources and lot
numbers of the ingredients, calculations, processes
used, results of any testing done, an assigned
beyond-use date, identification numbers, name of
the compounder, quantity of the preparation compounded and other pertinent information. It contains
all relevant information related to the actual compounding of the specific prescription. It is used for
checking the final preparation for accuracy.
Material Safety Data Sheets (MSDSs) may be either
hard copy or accessible electronically. They are
needed for all drug substances or bulk chemicals
located in the compounding pharmacy. If commercial products are used, the package insert can serve
this purpose.
QUALITY CONTROL
All the paperwork from the first step to the final
preparation should be reviewed along with observing the finished preparation.
Standard Operating Procedures (SOPs) are documents that describe how to perform routine tasks in
the environment of formulation development, purchasing, compounding, testing, maintenance,
materials handling, quality assurance and dispensing. They contain step-by-step instructions to
perform tasks reliably and consistently; including
how a task will be performed, who will do the task,
who is responsible, why it will be performed and
any limits associated with the task.
Verification, not validation, is what is required. Verification involves checking to ensure that all the
processes were appropriate and accurately performed. Validation is much more involved and
time-consuming.
PATIENT COUNSELING
As with any prescription, patient counseling is
important. It is especially important with compounded preparations where the beyond-use date
may be rather short. Patients should be counseled
about use, storage and evidence of instability (visual changes, odor, etc.).
SUMMARY
There is no question that the standards of the USP
serve to enhance patient safety and also protect the
pharmacist. There are many general chapters in the
USP that either directly or indirectly affect pharmacy compounding. The primary chapters are <795>
Pharmaceutical Compounding-Nonsterile Preparations, <797> Pharmaceutical Compounding
Compounding-Sterile Preparations, <1075> Good
Compounding Practices, and <1160> Pharmaceutical Calculations in Prescription Compounding.
2. U.S. Pharmacopoeial Convention, Inc. USP-Pharmacists’ Pharmacopeia, Rockville MD, U.S.
Pharmacopeial Convention, Inc., 2005, pp 408-413.
2. Today, the USP/NF standards are applicable to:
I.
pharmaceutical companies
II.
compounding pharmacies
III. health food/nutrition stores
A. I only
B.
III only
C.
I and II only
D. II and III only
E.
I, II and III.
7.
8.
3. The USP began to reorient its activities to include pharmacy
compounding again in:
A. 1965
B.
1970
C.
1975
D. 1980
E.
1985
4. The terminology applied to compounded prescriptions and the date
after which they should not be used are:
A. products, expiration date
B.
products, beyond use date
C.
preparations, expiration date
D. preparations, beyond use date
E.
none of the above
5. The ultimate responsibility for compliance with all the USP/NF
standards for compounding rest with the:
A. prescribing physician
B.
owner
C.
compounder
D. technician
E.
all the above
6. If no valid data is available for an aqueous, oral compounded suspension, the beyond use date to be applied is:
A. 24 hours at room temperature
B.
72 hours at refrigerated temperature
C.
1 week at room temperature
D. 2 weeks at refrigerated temperature
E.
6 months at refrigerated temperature
Which of the following is NOT on the checklist for acceptable strength,
quality and purity?
A. Have the physical and chemical properties and medicinal, dietary, and
pharmaceutical uses of the drug substances been reviewed?
B. Are the quantity and quality of each active ingredient identifiable?
C. Will the active ingredients be effectively absorbed, locally or systemically according to the prescribed purpose, from the preparation and
route of administration?
D. Has the bioavailability of the compounded preparation been demonstrated?
E. Were all calculations and measurements confirmed to ensure
that the preparation will be compounded accurately?
The purposes of the thirteen steps in the Compounding Process are to:
I. minimize errors
II. maximize the prescribers’ intent for the patient
III. provide shortcuts in compounding
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
9.
Which of the following records is where the information concerning
the ingredients used in compounding a prescription, such as the manufacturer, lot numbers, expiration dates of chemicals, are recorded?
A. formulation record
B. compounding record
C. material safety data sheet
D. certificate of analysis
E. none of the above
10. The purpose of the compounding standards of the USP are to:
I. ensure third party reimbursement
II. enhance patient safety
III. protect the pharmacist
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
11. My practice setting is:
a. Community-based
c. Hospital-based
b. Managed care-based
d. Consultant and other
12. The quality of the information presented in this article was:
a. Excellent b. Good
c. Fair d. Poor
13. The test questions correspond well with the information presented.
a. Yes
b. No
14. Approximately how long did it take you to read the Secundum Artem
article AND respond to the test questions?
______________________________________________________________
15. What topics would you like to see in future issues of Secundum Artem?
______________________________________________________________
Please print address clearly below OR
affix an address label here if available
Date__________________________
Name_____________________________________________________________________________________________________
Home Address _____________________________________________________________________________________________
City______________________________________________State______________ Zip___________________________________
Secundum
Artem
Current & Practical Compounding
Information for the Pharmacist.
USP Chapter <795>
Pharmaceutical Compounding - Nonsterile Preparations
GOALS AND OBJECTIVES
Goal: The goal of this article is to provide information on the historical development and practical implementation
of USP Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations.
Objectives: After reading and studying the article, the reader will be able to:
1. Discuss the history and development of the USP-NF and the USP-Pharmacists’ Pharmacopeia.
2. List the five questions that should be considered concerning each compounded prescription.
3. Discuss the difference between a “product” and a “preparation” as well as the difference between an “expiration date”
and a “beyond use date”.
4. Discuss the various sections of USP Chapter <795> and their application.
5. List the two basic reasons or intent for developing USP Chapter <795>.
INTRODUCTION
What is USP Chapter <795>? Why should compounders be familiar with it? Where did it come from?
From where did it derive its authority? Do I have to
follow it? What happens if I don’t? Is it really important? What if I have never had a problem before……do
I still need to comply with its standards? Who establishes these standards? Are they “set in stone” or do
they change over time? What is the relationship
between the USP and the U.S. government? What is
the relationship between the USP and the Food and
Drug Administration? Do the USP standards really
contribute to patient safety?
Primary State Licensure _____________________________________________________________________________________
License No._________________________________________________________________________________________________
Home Phone (
Copies of the individual USP Chapter <795>
Pharmaceutical Compounding-Nonsterile
Preparations or the new USP-Pharmacists’
Pharmacopeia, can be obtained online at
www.usp.org or by calling 1-800-227-8772.
NUMBER 4
Please circle the most appropriate answer for each of the following questions. There is only ONE correct answer per question.
1. The first U.S. Pharmacopeia was established in 1820 by a group of:
A. pharmacists.
B.
physicians.
C.
government agents.
D. state boards.
E.
physicians and dentists.
REFERENCES
1. Allen Jr LV, Popovich NG, Ansel HC. Ansel’s
Pharmaceutical Dosage Forms and Drug Delivery
Systems, 8th Ed. Baltimore MD, Lippincott,
Williams & Wilkins, 2005, pp 7-12.
VOLUME 13
Send this completed form in for CE credit Today!
)_________________________________ Bus. Phone (
) ____________________________________
Email Address:_____________________________________________________________________________________________
ACPE No. 748-000-05-001-H01
To receive credit, send completed registration form and test answer sheet (original or a photocopy of the page), *to: QUEST
EDUCATIONAL SERVICES, INC., P.O. BOX 1092, GROTON, CT 06340. One contact hour (0.1 CEU) awarded for a passing grade
of 70%. Please retain a copy for your records. Fee paid for by Paddock Laboratories, Inc. Participants will receive a statement of
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*Please note that QUEST EDUCATIONAL SERVICES, INC. will only issue credit to quizzes completed in one’s own handwriting. No quizzes
completed by others and duplicated for others will be graded.
All these are valid questions that deserve an answer.
As we travel from looking at where the pharmacopeias
came from and from where they derive their authority,
we will look at how the USP-NF shapes pharmacy
compounding and the pharmaceutical industry today.
Loyd V. Allen, Jr., Ph.D., R.Ph., Professor Emeritus,
University of Oklahoma, HSC College of Pharmacy,
Oklahoma City, OK 73190
Two things to keep in mind regarding the USP and
these chapters; the intent is to protect both the patient
AND the pharmacist. Protection of the patient is
addressed when these standards are followed and the
pharmacist when any adverse event might occur where
patient harm and/or litigation results.
BACKGROUND
Pharmaceutical compounding is the history of pharmacy,
spanning the past 5,000 years, until the early to mid
1900s when the pharmaceutical industry came into
being. There are many recorded writings of formulas
and methods of treating disease in pharmacy history
books. The standards for uniformity and quality in
pharmacy compounding started back in 1580 in Bergamo,
Italy, where the term “pharmacopoeia” was first used in
connection with a local book of drug standards. Many
pharmacopeias were developed on local, city and
Quest Educational Services Inc. is accredited by the
Accreditation Council for Pharmacy Education as a
provider of continuing pharmaceutical education.
ACPE No. 748-000-05-001-H01 (0.1 CEU)
This lesson is no longer valid for CE credit after 12/01/08.
COMPOUNDING RECORDS AND
VERIFICATION
DOCUMENTS
Formulation Record, Compounding Record,
MSDS File
State boards of pharmacy have record keeping
requirements that must be met. The following are
practical for quality purposes and to enable another
compounder to duplicate the preparation when prepared at a later time.
The formulation record generally will be either on
the computer system, or may be an individual new
prescription or request. This is where the process
starts. The formulation record can be used to prepare the documentation for the compounding
record.
The compounding record contains the sources and lot
numbers of the ingredients, calculations, processes
used, results of any testing done, an assigned
beyond-use date, identification numbers, name of
the compounder, quantity of the preparation compounded and other pertinent information. It contains
all relevant information related to the actual compounding of the specific prescription. It is used for
checking the final preparation for accuracy.
Material Safety Data Sheets (MSDSs) may be either
hard copy or accessible electronically. They are
needed for all drug substances or bulk chemicals
located in the compounding pharmacy. If commercial products are used, the package insert can serve
this purpose.
QUALITY CONTROL
All the paperwork from the first step to the final
preparation should be reviewed along with observing the finished preparation.
Standard Operating Procedures (SOPs) are documents that describe how to perform routine tasks in
the environment of formulation development, purchasing, compounding, testing, maintenance,
materials handling, quality assurance and dispensing. They contain step-by-step instructions to
perform tasks reliably and consistently; including
how a task will be performed, who will do the task,
who is responsible, why it will be performed and
any limits associated with the task.
Verification, not validation, is what is required. Verification involves checking to ensure that all the
processes were appropriate and accurately performed. Validation is much more involved and
time-consuming.
PATIENT COUNSELING
As with any prescription, patient counseling is
important. It is especially important with compounded preparations where the beyond-use date
may be rather short. Patients should be counseled
about use, storage and evidence of instability (visual changes, odor, etc.).
SUMMARY
There is no question that the standards of the USP
serve to enhance patient safety and also protect the
pharmacist. There are many general chapters in the
USP that either directly or indirectly affect pharmacy compounding. The primary chapters are <795>
Pharmaceutical Compounding-Nonsterile Preparations, <797> Pharmaceutical Compounding
Compounding-Sterile Preparations, <1075> Good
Compounding Practices, and <1160> Pharmaceutical Calculations in Prescription Compounding.
In the next issue, we will discuss the rationale
behind and the practical application of USP <797>.
2. U.S. Pharmacopoeial Convention, Inc. USP-Pharmacists’ Pharmacopeia, Rockville MD, U.S.
Pharmacopeial Convention, Inc., 2005, pp 408-413.
2. Today, the USP/NF standards are applicable to:
I.
pharmaceutical companies
II.
compounding pharmacies
III. health food/nutrition stores
A. I only
B.
III only
C.
I and II only
D. II and III only
E.
I, II and III.
7.
8.
3. The USP began to reorient its activities to include pharmacy
compounding again in:
A. 1965
B.
1970
C.
1975
D. 1980
E.
1985
4. The terminology applied to compounded prescriptions and the date
after which they should not be used are:
A. products, expiration date
B.
products, beyond use date
C.
preparations, expiration date
D. preparations, beyond use date
E.
none of the above
5. The ultimate responsibility for compliance with all the USP/NF
standards for compounding rest with the:
A. prescribing physician
B.
owner
C.
compounder
D. technician
E.
all the above
6. If no valid data is available for an aqueous, oral compounded suspension, the beyond use date to be applied is:
A. 24 hours at room temperature
B.
72 hours at refrigerated temperature
C.
1 week at room temperature
D. 2 weeks at refrigerated temperature
E.
6 months at refrigerated temperature
Which of the following is NOT on the checklist for acceptable strength,
quality and purity?
A. Have the physical and chemical properties and medicinal, dietary, and
pharmaceutical uses of the drug substances been reviewed?
B. Are the quantity and quality of each active ingredient identifiable?
C. Will the active ingredients be effectively absorbed, locally or systemically according to the prescribed purpose, from the preparation and
route of administration?
D. Has the bioavailability of the compounded preparation been demonstrated?
E. Were all calculations and measurements confirmed to ensure
that the preparation will be compounded accurately?
The purposes of the thirteen steps in the Compounding Process are to:
I. minimize errors
II. maximize the prescribers’ intent for the patient
III. provide shortcuts in compounding
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
9.
Which of the following records is where the information concerning
the ingredients used in compounding a prescription, such as the manufacturer, lot numbers, expiration dates of chemicals, are recorded?
A. formulation record
B. compounding record
C. material safety data sheet
D. certificate of analysis
E. none of the above
10. The purpose of the compounding standards of the USP are to:
I. ensure third party reimbursement
II. enhance patient safety
III. protect the pharmacist
A. I only
B. III only
C. I and II only
D. II and III only
E. I, II and III.
11. My practice setting is:
a. Community-based
c. Hospital-based
b. Managed care-based
d. Consultant and other
12. The quality of the information presented in this article was:
a. Excellent b. Good
c. Fair d. Poor
13. The test questions correspond well with the information presented.
a. Yes
b. No
14. Approximately how long did it take you to read the Secundum Artem
article AND respond to the test questions?
______________________________________________________________
15. What topics would you like to see in future issues of Secundum Artem?
______________________________________________________________
Please print address clearly below OR
affix an address label here if available
Date__________________________
Name_____________________________________________________________________________________________________
Home Address _____________________________________________________________________________________________
City______________________________________________State______________ Zip___________________________________
Secundum
Artem
Current & Practical Compounding
Information for the Pharmacist.
USP Chapter <795>
Pharmaceutical Compounding - Nonsterile Preparations
GOALS AND OBJECTIVES
Goal: The goal of this article is to provide information on the historical development and practical implementation
of USP Chapter <795> Pharmaceutical Compounding-Nonsterile Preparations.
Objectives: After reading and studying the article, the reader will be able to:
1. Discuss the history and development of the USP-NF and the USP-Pharmacists’ Pharmacopeia.
2. List the five questions that should be considered concerning each compounded prescription.
3. Discuss the difference between a “product” and a “preparation” as well as the difference between an “expiration date”
and a “beyond use date”.
4. Discuss the various sections of USP Chapter <795> and their application.
5. List the two basic reasons or intent for developing USP Chapter <795>.
INTRODUCTION
What is USP Chapter <795>? Why should compounders be familiar with it? Where did it come from?
From where did it derive its authority? Do I have to
follow it? What happens if I don’t? Is it really important? What if I have never had a problem before……do
I still need to comply with its standards? Who establishes these standards? Are they “set in stone” or do
they change over time? What is the relationship
between the USP and the U.S. government? What is
the relationship between the USP and the Food and
Drug Administration? Do the USP standards really
contribute to patient safety?
Primary State Licensure _____________________________________________________________________________________
License No._________________________________________________________________________________________________
Home Phone (
Copies of the individual USP Chapter <795>
Pharmaceutical Compounding-Nonsterile
Preparations or the new USP-Pharmacists’
Pharmacopeia, can be obtained online at
www.usp.org or by calling 1-800-227-8772.
NUMBER 4
Please circle the most appropriate answer for each of the following questions. There is only ONE correct answer per question.
1. The first U.S. Pharmacopeia was established in 1820 by a group of:
A. pharmacists.
B.
physicians.
C.
government agents.
D. state boards.
E.
physicians and dentists.
REFERENCES
1. Allen Jr LV, Popovich NG, Ansel HC. Ansel’s
Pharmaceutical Dosage Forms and Drug Delivery
Systems, 8th Ed. Baltimore MD, Lippincott,
Williams & Wilkins, 2005, pp 7-12.
VOLUME 13
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ACPE No. 748-000-05-001-H01
To receive credit, send completed registration form and test answer sheet (original or a photocopy of the page), *to: QUEST
EDUCATIONAL SERVICES, INC., P.O. BOX 1092, GROTON, CT 06340. One contact hour (0.1 CEU) awarded for a passing grade
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completed by others and duplicated for others will be graded.
All these are valid questions that deserve an answer.
As we travel from looking at where the pharmacopeias
came from and from where they derive their authority,
we will look at how the USP-NF shapes pharmacy
compounding and the pharmaceutical industry today.
Loyd V. Allen, Jr., Ph.D., R.Ph., Professor Emeritus,
University of Oklahoma, HSC College of Pharmacy,
Oklahoma City, OK 73190
Two things to keep in mind regarding the USP and
these chapters; the intent is to protect both the patient
AND the pharmacist. Protection of the patient is
addressed when these standards are followed and the
pharmacist when any adverse event might occur where
patient harm and/or litigation results.
BACKGROUND
Pharmaceutical compounding is the history of pharmacy,
spanning the past 5,000 years, until the early to mid
1900s when the pharmaceutical industry came into
being. There are many recorded writings of formulas
and methods of treating disease in pharmacy history
books. The standards for uniformity and quality in
pharmacy compounding started back in 1580 in Bergamo,
Italy, where the term “pharmacopoeia” was first used in
connection with a local book of drug standards. Many
pharmacopeias were developed on local, city and
Quest Educational Services Inc. is accredited by the
Accreditation Council for Pharmacy Education as a
provider of continuing pharmaceutical education.
ACPE No. 748-000-05-001-H01 (0.1 CEU)
This lesson is no longer valid for CE credit after 12/01/08.